Recombinant Human Ficolin-3 Protein, CF

Human Ficolin-3 (fibrinogen/collagen-like), also called H-ficolin and, previously, Hakata antigen or thermolabile beta-2 macroglycoprotein, is a member of the ficolin family of secreted pattern recognition proteins that belong to the lectin complement activation pathway (1, 2). Ficolin-3 is expressed by bile duct epithelial cells and hepatocytes, and is released into the bile and circulation, where it averages 18 μg/mL (3, 4). It is also secreted by bronchial and alveolar epithelial cells in the lung (3). Mature human Ficolin-3 shares 46% and 52% amino acid (aa) identity with human Ficolin-1 and Ficolin-2, respectively. Ficolin-3 has only been identified in primates and is likely a pseudogene in other species (5). The 35 kDa, 288 aa human Ficolin-3 (isoform 2) contains a signal sequence, an N-terminal collagen domain and a C-terminal fibrinogen-like domain that includes a calcium binding site and two potential N-glycosylation sites. Isoform 1 contains an additional 11 aa between the collagen and fibrinogen-like domains. The collagen domain mediates trimer formation, and a ~650 kDa, 18 subunit oligomer is formed by disulfide links at the N-terminus (2, 6, 7). Ficolin-3 binds a limited set of carbohydrates containing mannose, galactose or D-fucose (2, 6). Binding of microbial carbohydrates has been clearly demonstrated only for the PSA antigen of Aerococcus viridans (4, 8, 9). Pathogen recognition initiates an immune response involving the calcium-dependent interaction of Ficolin-3 with the MBL-associated serine protease (MASP) complex. This cleaves C4 to activate the complement pathway (4, 9). In a secondary role, Ficolins 2 and 3 bind apoptotic cells, activating complement cascades that assist in clearance of the cells (10). Circulating antibodies to Ficolin-3 have been identified in systemic lupus erythematosus (7).